The U.S. Food and Drug Administration on Wednesday released draft guidance aimed at helping drug developers validate alternatives to animal testing, signaling a continued shift toward human-centered approaches in evaluating drug safety and effectiveness.

The guidance focuses on the use of new approach methodologies, or NAMs, which rely on advanced scientific tools to generate data that may replace traditional animal studies, according to a news release. Officials said the move is intended to help bring safe and effective treatments to market more quickly while improving how drugs are evaluated before clinical trials.

“This draft guidance advances our commitment to replace animal testing with human-relevant, scientifically rigorous methods” said HHS Secretary Robert F. Kennedy Jr. in the release. “Clear validation expectations will help modern tools earn regulatory confidence and speed safer, more effective therapies to patients.”

The announcement marks another step in the agency’s broader roadmap to reduce reliance on animal testing, which has long been the default method for generating nonclinical pharmacology and toxicology data required before human trials can begin. While animal studies remain common, the FDA’s Center for Drug Evaluation and Research already reviews NAMs data when the approaches demonstrate reliability and scientific validity.

"Technological advances are allowing us to move beyond animal testing in drug development, which has a poor track record of predicting safety and efficacy in humans," said FDA Commissioner Marty Makary, M.D., M.P.H. "This guidance will facilitate the adoption of modern alternatives to animal testing in regulatory submissions."

The release said NAMs include a range of emerging tools such as laboratory-based in vitro studies, three-dimensional models like organoids and organs on chips, chemical reactivity testing, computer simulations and studies involving simpler organisms such as zebrafish or C. elegans. In some cases, validated NAMs have already shown stronger predictive value for human responses than traditional animal models.

Regulators say these approaches can help identify potential toxicities, explain how drugs work and improve the overall predictability of nonclinical research, ultimately enhancing patient safety in clinical trials.

The draft guidance outlines four key principles for validating NAMs. These include clearly defining the method’s intended regulatory use, demonstrating its relevance to human biology, establishing technical reliability through reproducible data and ensuring the method is fit for regulatory decision-making such as drug approval reviews.

“It is time for the FDA to shift the drug development paradigm away from the current default of using animals to predict human responses to one where these data are obtained through human-centric models which can more reliably, efficiently and ethically predict human drug reactions prior to clinical trials,” said Acting CDER Director Tracy Beth Hoeg, M.D., Ph.D.

While the document provides general recommendations, it does not address specific technologies or drug applications. The FDA is encouraging developers to consult with agency review divisions when considering NAMs, particularly for disease-specific or organ-specific uses.

The expanded use of these methods aligns with recommendations from the MAHA Commission, which called for reducing reliance on animal studies that often fail to replicate complex human conditions. The guidance also follows a December 2025 draft policy aimed at reducing the use of non-human primates in testing certain monoclonal antibodies.

In a related action, the FDA announced a level 2 revision to its final guidance, “Guidance for Industry Pyrogen Endotoxins Testing – Questions and Answers,” clarifying its current approach to endotoxin testing. The update aligns with USP Chapter ⟨86⟩ on bacterial endotoxins testing using recombinant reagents, published in May 2025, and is intended to support manufacturers transitioning away from traditional animal-based methods.

More information on the endotoxin testing guidance is available at www.fda.gov, along with details on the draft NAMs guidance and related updates.